The Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) plays a vital role in the control of neuronal neurotransmitter release and membrane excitability. The modulation of Ca2+ channels controls the extent of Ca2+ entry and provides a way of regulating neuronal function. Multiple classes of VGCCs exist in both peripheral and central mammalian neurons, based on biophysical and pharmacological identification. Electrophysi-ological studies have described a low voltage-activated T-type current and several pharmacologically defined high voltage-activated currents on neuronal cell bodies such as the L, N, P, Q, and R-type Ca2+ channels (1-3). L-type channels are sensitive to the dihydropyridines (e.g., nifedipine), N channels to ra-conotoxin-GVIA, P channels to ra-agatoxin-IVA, Q-type to ra-conotoxin-MVIIC, and an R-type insensitive to all these antagonists (1-3).
The presence and action of both endogenous and synthetic steroids in the mammalian central nervous system (CNS) are well-documented. These neuroactive steroids, including those synthesized in brain (neurosteroids and their sulfate derivatives), have a rapid and direct excitatory or inhibitory action on neuronal membranes that is independent of nuclear transcription (4). Considerable data has emerged demonstrating that some neuroactive steroids can potentiate or inhibit GABAA-activated Cl- current (GABA), enhance NMDA receptor-mediated excitatory amino acid responses, inhibit glycine-activated Cl- channels, and inhibit voltage-dependent Ca2+ channels (5-9).
From: Contemporary Endocrinology: Neurosteroids: A New Regulatory Function in the Nervous System Edited by: E.-E. Baulieu, P. Robel, and M. Schumacher © Humana Press Inc., Totowa, NJ
Fig. 1. Neuroactive steroid inhibition of whole-cell Ca2+ channel current in freshly isolated guinea-pig hippocampal CA1 neurons and rat hypothalamic ventromedial nucleus (VMN) neurons. (A) The neurosteroid pregnenolone sulfate (PREGS) inhibition of the Ca2+ channel current, which was fully reversible with wash (not shown) in a CA1 neuron. (B) The neurosteroid tetrahydrodeoxycorticosterone (3a,5a-THDOC) inhibition of the Ca2+ channel current in a VMN neuron. (C) The neuroactive steroid medroxyprogesterone acetate (MP; a progesterone derivative) inhibition of the Ca2+ channel current in a VMN neuron. (D) The steroid progesterone (PROG) had a minimal effect (8% inhibition peak current), which was reversible with wash. All neurons were freshly isolated as previously described; Ca2+ channel currents were evoked by 200 ms steps from a holding potential of -80 mV to a test potential of -10 mV with the individual (leak subtracted) currents recorded at -10 mV illustrated, as previously described (11).
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